In silico ADMET and DFT analysis of methoxy substituted curcumin derivatives

The current study aimed to predict drug ability of methoxy group substituted curcumin derivatives (MC1 to MC4) using ADMETLab 3.0 and DFT approaches. Almost all derivatives exhibited satisfactory physicochemical properties and medicinal chemistry. Pharmacokinetic profile revealed that all derivatives showed higher Caco-2 cell predicted permeability and exhibited a P-glycoprotein (Pgp) inhibitor capability, while non-of them is a Pgpsubstrate. MC1 and MC2 exhibited favorable human intestinal absorption (HIA) values. MC1 was in favor of better oral bioavailability. Values for plasma protein binding and volume of distribution were optimum for MC1 and MC2. All compounds were unable to cross blood brain barrier. Fraction unbound in the plasma was moderate for all compounds. All derivatives exhibited moderate clearance rate, while having ultra short half-lives. Toxicity profile was moderate for almost all compounds. Similarly, the DFT computations of the compounds of the curcumin derivatives were conducted at B3LYP/6-311G** level to predict and then assess the key electronic characteristics underlying the bioactivity. Accordingly, the MC4 molecule (Delta Egap = 3.883 eV) would prefer to interact with the external molecular system more than the other molecules due to having the biggest energy gap. The Delta Nmax (2.328 eV) and Delta epsilon back-donat. (-0.422 eV) scores implied that MC1 would have more charge transfer capability and the lowest stability via back donation among the compounds. In short, the derivative (MC1 to MC4) exhibited strong extrinsic therapeutic properties and therefore stand eligible for further in vitro and in vivo studies.